a) Field of the Invention
This invention relates to block copolymers useful in diagnostic imaging, drug delivery, and as drugs.
b) Information Disclosure Statement
Nathen et al, Bioconjugate Chemistry 4 54-62 (1993) discloses copolymers of lysine and polyethylene glycol prepared by reacting amino groups of lysine with activated ester derivatives of polyethylene glycol. The polymer is best described as a polyamide formed by .epsilon.-amino and the .alpha.-amino of lysine.
Davis et al., U.S. Pat. No. 4,179,337 dated Dec. 18, 1979 discloses insulin coupled to polyethylene glycol or polypropropylene glycol having a molecular weight of 500 to 20,000 molecular weight.
Zilkha et al, U.S. Pat. No. 3,441,526 issued Apr. 29, 1969 discloses N-carboxyanhydride-based polymerization of polypeptide with polyethylene glycol, no examples of the preparation are given.
British Patent 1,469,472 discloses low molecular weight polyethylene oxide immobilized proteins, said to have low immunogenicity.
However, none of these references suggests a linear block copolymer having repeating units of an alkylene oxide linked to repeating units of a peptide through a linking group formed by the reaction of an amine precursor and an epoxide precursor. Moreover, the prior art teaches that crosslinking (via amino acid side chains) often frustrates the linear copolymerization often sought. The invention described herein advantageously avoids such crosslinking.